Platelet-derived extracellular vesicles promote the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes via CXCR2 signaling

Platelet-derived extracellular vesicles (PEVs), which are generated from the plasma membrane during platelet activation, may be involved in the inflammatory processes of rheumatoid arthritis (RA). The motility of RA fibroblast-like synoviocytes (RA-FLS) plays a key role in the development of synovial inflammation and joint erosion. However, the effects of PEVs on the motility of RA-FLS remain unclear. Thus, the present study aimed to investigate the active contents and potential molecular mechanisms underlying the role of PEVs in regulating the migration and invasion of RA-FLS. The results demonstrated that PEVs contain certain chemokines associated with cell migration and invasion, including C-C motif chemokine ligand 5, C-X-C motif chemokine ligand (CXCL)4 and CXCL7. Furthermore, SB225002, an antagonist of C-X-C motif chemokine receptor 2 (CXCR2; a CXCL7 receptor), partially prevented the migration and invasion of RA-FLS induced by PEVs, suggesting that PEVs may activate a CXCR2-mediated signaling pathway in RA-FLS. In addition, SB225002 antagonized the phosphorylation of IκB and NF-κB in RA-FLS induced by PEVs. Taken together, the results of the present study suggested that PEVs may promote the migration and invasion of RA-FLS by activating the NF-κB pathway mediated by the CXCR2 signaling pathway.